OXIDATIONS OF ALCOHOLS

OXIDATION OF AN ALCOHOL
( LOSS OF 2H+ and 2e- )

a-carbon

- 2H

O H

OXIDATION REDUCTION

+ 2H

a-hydrogen

LOSS OF TWO HYDROGENS

one an a-H

Oxidations
The alcohol must have a-hydrogens.

H R C OH H H R C OH R' R'' R C OH R' R R

O C H R

O C OH

O C R' O
no reaction

Remember: A dehydrogenation (loss of hydrogen) is also a form of oxidation!

MANTRA
Primary alcohols oxidize to give Carboxylic acids (via aldehyde)* Seconday alcohols oxidize to give Ketones

Tertiary alcohols do not oxidize no oxidation Aldehydes oxidize easily to give Carboxylic acids
* With special reagents, the oxidation of a primary alcohol
can be stopped at the aldehyde.

PRIMARY ALCOHOLS

Oxidation of Primary Alcohols with KMnO4

R CH2 OH KMnO4 heat O R C H KMnO4 heat O R C OH
+ MnO2
precipitate C=C Double bonds are also oxidized by this reagent.
REQUIRES HEAT

two a-hydrogens

Oxidation of Primary Alcohols with K2Cr2O7

CHROMIC ACID TEST

K2Cr2O7 R CH2 OH H2SO4

O R C H K2Cr2O7 H2SO4 O R C OH 3+ + Cr

SECONDARY ALCOHOLS

Oxidation of Secondary Alcohols

CHROMIC ACID TEST

OH R C R H

K2Cr2O7 H2SO4

O R C R 3+ Cr

Jones Oxidation

JONES REAGENT

CHROMIC ACID
EQUILIBRIA

H2SO4 CrO3 + H2O H2CrO4 O

H2SO4 x2 H2Cr2O7 + H2O O O O O

H O Cr O H O
Chromic acid

H O Cr O Cr O H
Dichromic acid

ALL OF THESE ARE CHROMIC ACID SPECIES

CrO3 H2SO4

H2CrO4 H2SO4

NaCr2O7 H2SO4

oxidizing agents

O HO Cr OH O
H 2O H2SO
4

MECHANISM

Alcohols react with chromic acid to form chromate esters.

HO Cr O : + H H O .. R C O: H H
Primary alcohol has two a-H

.. .. R C O Cr O H .. ..
H O
Chromate ester

MECHANISM

( continued )
aldehyde

.. .. R C O Cr O H .. ..
H H O: H O

.. :Cr O H ..
O
The two lost electrons end up here.

R C O: H

..

..

Loss of two electrons Loss of a-hydrogen

H O: + H

FIRST OXIDATION

Oxidation continues
(next slide)

MECHANISM

( continued )

Requires water and acid

H R C O

H O

hydrate
(an alcohol !)

R C O H 2O H H

Oxidation continues because the aldehyde forms a hydrate. The hydrate is an alcohol (diol) that has an a-hydrogen. Oxidation continues

MECHANISM
O H H HO Cr O : + H H O .. R C O: H O :.. H
hydrate

( continued )
H

:O H ..
O O

.. .. R C O Cr O H .. ..
OH

Chromate ester

Loss of a-hydrogen, loss of 2 electrons.

Carboxylic acid

R C O:

..

OH

.. : Cr O H ..
O

SECOND OXIDATION

.. H
H O+ H

HOW CAN WE

STOP OXIDATION OF THE ALDEHYDE ?

Oxidation of the aldehyde requires the hydrate to form.
H R C O H 2O H
+

H R C O O H H

Formation of the hydrate requires acid and water.

What if we do the reaction in basic medium with no water ?

SARRETT AND PCC REAGENTS

Oxidation with Chromic Oxide and Pyridine

OH R C R H CH2Cl2
aldehydes do not oxidize further

CrO3 . N

O R C R

Sarett Oxidation

Oxidation with Pyridinium Chlorochromate

CrO3Cl . OH R C R H CH2Cl2
aldehydes do not oxidize further

O R C R

PCC Oxidation

except in DMF which enhances reactivity

MEERWEIN-PONNDORF-VERLEY REDUCTION

MEERWEIN-PONNDORF-VERLEY REDUCTION
aluminum isopropoxide

O R C
+ H C 3 R

OH C CH3 H
isopropyl alcohol

Al(OiPr)3

OH R C R H
+

O H3C C CH3

acetone

EQUILIBRIUM
Use an excess of isopropyl alcohol to reduce a ketone. Use an excess of acetone to oxidize an alcohol.

O O R C

Al O O CH3 H CH3

HYDRIDE DONOR

The alcohol complexes with the aluminum isopropoxide and acts as a hydride donor to the ketone.

TOLLENS TEST

The Tollens Test

O R C H 2 Ag(NH3)2OH R O C O NH4 +
+

metallic silver

2 Ag

aldehyde

+ H2O + NH3

Ketones do not react.

silver mirror

Remember that aldehydes are easily oxidized.

CARBOHYDRATES
AND THE TOLLENS TEST aldehyde

H
OH H2C HO HO OH H O OH

O OH H OH OH

H HO H H

The open chain form is an aldehyde and gives a Tollens test. REDUCING SUGAR

b-D-(+)-glucopyranose
Pyranose and open-chain forms are in equilibrium in solution.

CH2 OH
D-(+)-glucose

CARBOHYDRATES
AND THE TOLLENS TEST TAUTOMERIZATION ketone aldehyde

H
CH2 OH C O HO H H H OH OH CH2 OH
D-(-)-fructose

CH OH C OH HO H H H OH OH CH2 OH
enediol

* CH OH

HO H H

H OH OH CH2 OH

* both diastereomers REDUCING SUGAR

a-D-(-)-fructofuranose
Ketoses also give the test because they tautomerize! in solution.

CARBOHYDRATES
AND THE TOLLENS TEST hemiacetals open in solution = REDUCING SUGAR
H

OH H2C HO HO OH OH H2C HO HO OH H O OMe H O OH

H HO H H

O OH H OH OH

aldehyde

CH2 OH

ketoses tautomerize to reducing sugars

acetals do not open in solution unless hydrolyzed in acid

= NONREDUCING SUGAR

AND THE TOLLENS TEST Any polysaccharide which has a hemiacetal ring will give a positive Tollens test = reducing sugar.
CH2OH H H OH HO H OH O H O OH H H a b CH2OH O H HO CH2OH H

CARBOHYDRATES

(+)-Sucrose non-reducing Neither sugar is in a hemiacetal link.

CH2OH H O OH H HO H OH O b H H

CH2OH O c OH H a H OH H OH
Maltose reducing sugar Hemiacetal link at a.

SYNTHESIS PROBLEMS

A Simple Synthesis Problem

O C CH 2

Make from benzyl alcohol

complete synthesis on board

A Synthesis Problem
O CH3 C OH

O CH3 C CH3

complete synthesis on board

Yet Another Conversion

H3C CH OH H3C

H3C C CH CH2 CH3 H3C

+ H3C CH2 CH2 OH

complete synthesis on board

SYNTHESIS OF TRIPHENYLMETHANOL

Br

C OH

a) b) c) d)

via benzoyl chloride via benzaldehyde via benzyl alcohol via benzophenone

H3C H3C

CH3 H

CONVERSIONS

CH3 H3C C COOH CH3

CH3 H3C C CHO CH3

CH3 O CH3 H3C C CH2OH CH3 H3C C CH3 C CH3

Another Synthesis Problem

O C H

C CH2

complete synthesis on board

PHARMACEUTICALS
Mexican Yams
OH HO C CH

the pill
Norethisterone

must be injected

CH3

better absorbed through the stomach and intestines than progesterone

STEROID
O

C D

progesterone

A B

Mexican Yams
OH OH

HOCH2CH2OH

CrO3 pyridine

H+ (-H2O)
O O O O

acetal
protecting group

HO

C CH

Na C CH NH3(liq) O Na

H3

O+

C CH

O O

norethisterone